alpha-actinin-2 is a new component of the dystrophin-glycoprotein complex

The human skeletal muscle yeast two-hybrid cDNA library was screened with t he carboxyl-terminal region (the last 200 amino acids) of dystrophin. Two i nteracting clones were identified corresponding to alpha-actinin-2 and acti n. Interactions between alpha-actinin, actin, and dystrophin were confirmed by the ligand-blotting technique, by colocalization of dystrophin and alph a-actinin-2 to the isolated skeletal muscle sarcolemmal vesicles and to the plasma membranes isolated from C2C12 myoblasts, and by indirect immunoloca lization of dystrophin and alpha-actinin-2 in skeletal muscle cells. This i s the first identification of a direct interaction between alpha-actinin, a ctin, and the carboxyl-terminal region of dystrophin. We propose that dystr ophin forms lateral, multicontact association with actin and that binding o f alpha-actinin-2 to the carboxyl-terminus of dystrophin is the communicati on Link between the integrins and the dystrophin/dystrophin-glycoprotein co mplex. (C) 1999 Academic Press.